Tetanus (Clostridium tetani) imp
Etiology:
Caused by Clostridium tetani, a spore-forming anaerobic bacillus.
Infection occurs after puncture wounds or contaminated injuries. هاي بتكون بالسؤال
Unvaccinated individuals are at highest risk.
Pathogenesis:
Disease due to tetanospasmin, a metalloprotease exotoxin (not tissue invasion).
Mechanism:
IMPORTANT
Toxin binds to presynaptic membranes of peripheral motor neurons. مهم
Travels retrograde via axons to CNS inhibitory neurons (spinal cord & brainstem).
Blocks release of inhibitory neurotransmitters:
VERY IMPORTANT
Glycine
GABA
Loss of inhibition → uncontrolled motor neuron firing.
Clinical Features:
بتكون بالسؤال
Muscle spasms and hyperreflexia
Trismus (lockjaw)
Risus sardonicus (fixed grin)
Opisthotonos (arched back)
Tetanic spasms triggered by minor stimuli (touch, sound, light)
Irritability and autonomic instability may occur.
Reye syndrome
Reye syndrome should be suspected in a young child with acute liver failure and encephalopathy after receiving aspirin for a virus-induced fever.
IMPORTANT
Aspirin in this setting is a mitochondrial toxin that leads to hepatic steatosis, hyperammonemia, and diffuse astrocyte swelling (ie, cerebral edema).
Toxoplasma encephalitis
Setting
Exposure to cat feces with subsequent ingestion
of Toxoplasma gondii (or when patients ingest undercooked meat from an intermediate host (eg, pig, sheep).)
Reactivation in setting of immunosuppression
Primarily AIDS with CD4 count <100/mm3
Clinical
Headache
Confusion
Fever
Focal neurologic deficits/seizures
Diagnostic
Positive Toxoplasma gondii IgG
Multiple ring-enhancing brain lesions VERY IMPORTANT
Therapeutic
Sulfadiazine & pyrimethamine (leucovorin)
Antiretroviral initiation
Prophylaxis: TMP-SMX (CD4 count <100/mm3)
TMP-SMX = trimethoprim-sulfamethoxazole.
Toxoplasmosis
1.Chorioretinitis
2.Hydrocephalus
3.Diffuse intracranial calcifications
Cryptococcus neoformans
THE IMPORTANT THINGS :
1.BUDING (ROUND) YEST
2.AIDS + IMMUONOCOMPRAMISED
3.RS TRANSMISSION (LUNG) BY BIRD DROPPING CONTAMINATED SOIL ,
4.DX: INDIAN INK STAIN OF CSF Latex agglutination
5.THICK POLYSACCHARIED CAPSULE (clear areas on H&E tissue stain shown above)
6.TX: Amphotericin B
Morphology
Yeast with a polysaccharide capsule
Round/oval cells with narrow-based buds
Epidemiology
Soil and pigeon droppings
Respiratory transmission
Opportunistic infection in patients with AIDS (CD4 <100/mm3)
Infection
Meningoencephalitis: Progressive headache, fever, confusion
Possible disseminated disease
HOW?
Replication of C neoformans in the brain clogs the arachnoid villi with yeast antigens and capsular proteins, leading to obstructed cerebrospinal fluid outflow. This elevates intracranial pressure
Diagnosis
India ink stain of cerebrospinal fluid
Latex agglutination of cerebrospinal fluid
Culture using Sabouraud agar
Treatment
Amphotericin B and flucytosine (induction)
Fluconazole (maintenance)
HSV encephalitis
NOTE
HSV 1 → ENCEPHALITIS (TEMPORAL)
HSV2 → MANINGITIS
Pathogenesis
HSV-1 → olfactory tract → olfactory cortex (temporal lobe) VERY IMPORTANT
Presentation
Fever, headache, seizures, aphasia, mental status/behavior changes لاحظ بيتخربط حكيه وتصرفاته
Diagnosis
Temporal lobe hemorrhage/edema on brain imaging AGAIN IMPORTANT
Cerebrospinal fluid PCR for HSV
Treatment
Intravenous acyclovir
meningitis
Common microbes:
1.Enteroviruses (most common) VERY IMPORTANT
(eg, coxsackievirus, echovirus, poliovirus)
2.Arboviruses (BY mosquitoes)
3.Herpes simplex virus type 2 (HSV2)
CSF cell differential:
WBC count often <500/mm3
Lymphocytic predominance
Glucose levels are normal or slightly reduced
Protein generally <150 mg/dL
Adults: S. pneumoniae & N. meningitidis
Neonates: GBS & gram-negative bacilli
AIDS,OLD: LISTERIA
WBC count often >1,000/mm3
Glucose levels <45 mg/dL
Protein is often >250 mg/dL
CSF Gram stain & culture:
Often positive for a specific organism
Neisseria meningitidis
IMPORTANT:
1.Pharynx → blood → choroid plexus → meninges
2.CAPSULAR POLYSACCARIDE VACCINE
VS 3.Lipooligosaccharide, a virulence factor in the pathogen’s outer membrane, is the major underlying cause of disease severity.
1.(gram-negative diplococcus)
2.transmitted via aerosolized droplets and are able to colonize the nasopharynx IMPORTANT
3.Due to the presence of specialized surface components (eg, fimbriae, pili)
4.asymptomatic carrier state, but in a minority of patients the bacteria penetrate the epithelium and enter the bloodstream.
Intravascular survival is dependent on capsular polysaccharides, which allow the bacteria to evade destruction by the alternative complement system. 5.Meningitis occurs when the bacteria penetrate the cerebral capillary endothelium or the choroid plexus, the location of blood-CSF barrier.
6.anti‑pili antibodies reduce colonization and carrier state, thereby lowering disease risk. (VACCINE)
7.Pili undergo extensive antigenic variation (e.g., phase variation on–off switching, intragenomic recombination, horizontal gene transfer), limiting the effectiveness of vaccines that target pili.
- OTHER VURULANCE FACTORS :
Other prominent N meningitidis virulence factors include IgA protease (destroy mucosal antibodies that would otherwise inhibit epithelial colonization), capsular polysaccharides (prevent phagocytosis and phagolysosome destruction), lipo-oligosaccharide (an endotoxin that is the major source of toxicity), and opacity proteins (aid in endothelial attachment and invasion).
Rabies
ACH RECEPTOR , PHARYNGEAL SPASM, HYPERSALIVATION, FEVER AND MALAISA
1.Rhabdoviridae family
2.contaminated saliva from an infected animal (eg, dog, bat)
3.has a bullet-shaped envelope with knob-like glycoproteins that bind to nicotinic acetylcholine receptors. VERY IMPORTANTTTT
- The virus replicates locally within the muscle tissue of the bite wound for several days or weeks and then travels in a retrograde fashion through peripheral nerve axons to the dorsal root ganglia. From there, it rapidly ascends the spinal cord and infects the diencephalon, hippocampus, and brain stem.
Patients initially develop a nonspecific flu-like prodrome (fever, malaise, myalgias); paresthesias radiating proximally from a known wound site can be an important clue.
5.When the virus enters the CNS, the infection typically evolves into rabies encephalitis, which is characterized by painful pharyngeal spasms leading to avoidance of water (hydrophobia), mental status changes, muscular rigidity, and autonomic dysfunction (pupil dilation, hypersalivation).
6.Once symptoms of rabies encephalitis appear, postexposure prophylaxis is no longer effective and nearly all patients die.
West Nile virus
IMPORTANT:
1.ASYMMATRIC FLACCID PARALYSIS
2. BY Mosquitoes (harbored in birds)
3.IMMUONOCOMPRAMISED +AIDS
4.
Clinical syndrome
West Nile fever: fever, headache, rash (maculopapular/morbilliform)
Neuroinvasive: meningitis, encephalitis, acute asymmetric flaccid paralysis IMPORTANT
Parkinsonian symptoms (eg, rigidity, bradykinesia, tremor)
OR FLU LIKE OR ASYMPTOMATIC IN HEALTHY PEOPLE
Transmission
Mosquitoes (Culex spp.)
More common in summer/fall
Warm climate (southern United States, Latin America, Africa)
Risk factors
Older age
Malignancy/organ transplant
Listeria
CONTAMINATED FOOD , AMPICILLIN
Listeria can multiply in cold temperatures (4-10 C), a unique feature that allows it to grow well in refrigerated foods.
Listeriosis most often occurs in immunocompromised adults (eg, renal transplantation, hematologic malignancy).
The bacteria can access the bloodstream following ingestion of contaminated food (eg, unpasteurized milk and milk products, undercooked meats, unwashed raw vegetables) and cause bacteremia and meningoencephalitis.
Ampicillin is the antibiotic of choice
Guillain-Barré syndrome
SYMMETRIC ACINDING WEAKNESS , TRIGGERING EVENT (CJ
,VIRUSES ,VACCINES )
Mechanism
Immune-mediated polyneuropathy due to cross-reacting antibodies (molecular mimicry)
Triggering events VERY IMPORTANTT
Campylobacter jejuni
Viral illness (eg, HIV, upper respiratory viral illness)
Trauma/surgery
Vaccinations
Pathology
Endoneurial inflammation
Segmental demyelination & axon damage
Manifestations
Symmetric, progressive muscle weakness
Depressed deep tendon reflexes
Paresthesias; back pain
Respiratory compromise
Ameba
IMPORTANT :WARM FRESH WATER
penetrates NASLA MUCOSA ,migrates in a retrograde fashion through the OLFACTORY NERVE to the brain.
Primary amebic meningoencephalitis is a rare, highly fatal condition caused by the free-living, flagellated protozoan Naegleria fowleri. This pathogen resides in warm fresh water (30-45 C) and moist soil. Humans are primarily exposed when the organism comes into contact with nasal mucosa during recreational water activities (eg, swimming, diving, water skiing, unchlorinated hot tub bathing).
Patients typically have rapidly progressive meningeal signs, cranial nerve deficits, and confusion.
Cerebrospinal fluid analysis with wet mount can usually identify motile trophozoites. Although treatment should be attempted, almost all patients die within 2-3 days.
Botulinum toxin
Clostridium botulinum :
1.CANNED FOOD
2.PRESYNAPTIC ACH RELEASE (vesicles)
3.CN DEFICIT :(diplopia, dysphagia, dysphonia [3Ds])
4.DESCENDIN SYMMATRIC PARALYSIS
5.A SPORE FORMING gram-positive, anaerobic bacillus that synthesizes botulinum toxin,
Botulinum toxin blocks the presynaptic exocytosis of ACh vesicles, causing impaired muscarinic and nicotinic neurotransmission.
It characteristically presents as a symmetric descending paralysis that manifests with cranial nerve abnormalities, often following consumption of home-canned foods.
The toxin is heat labile, so disease can be prevented by thoroughly heating food prior to consumption.
Botulinum toxin can be used to treat focal dystonia and other disorders of abnormal muscle contraction.
